Abstract

A108

Background: Pancreatic cancer is the fifth leading cause of cancer death in the United States. Therefore, novel therapeutic agents that can inhibit signaling pathways implicated in the proliferation and survival of pancreatic cancer cells are of interest. Tocotrienols are members of the vitamin E family but, unlike tocopherols, possess an unsaturated isoprenoid side-chain that confers superior anti-cancer properties like inhibition of the HMG Co A reductase and NFκβ pathways. Other pathways relevant to pancreatic carcinogenesis may also be modulated. Methods: Pancreatic cancer cells (Panc-1, Panc-28, MiaPaca-2 and BXPC-3) were treated with 0-100 ∝M of γ- and δ-tocotrienol and tocopherol for 24hrs for MTT cell viability assay. After obtaining IC50 dose, same cell lines were treated with 80 ∝M of γ- and δ-tocotrienol and tocopherol for 12 hrs for Western blotting. Results: Our studies indicate that both tocotrienols induced cell death (> 80 %) by the MTT cell viability assay in all four cell lines. We also examined the effects of the tocotrienols on the Akt and the Ras/Raf/MEK/ERK signaling pathways. γ- and δ-Tocotrienol treatment of cells reduced the activation of ERK MAP kinase and its downstream mediator RSK (ribosomal protein S6k) in addition to suppressing the activation of protein kinase Akt. These effects were observed in response to tocotrienols and not tocopherols. Conclusions: Tocotrienol isoforms of vitamin E can induce apoptosis in pancreatic cancer cells through the suppression of vital cell survival signaling pathways such as those mediated by the Akt and ERK/MAP kinases. Molecular bases for these effects are being investigated.